Decreased GnRH, but increased FSH and LH levels, have been observed during reproductive aging in women and some species of laboratory animals. These paradoxical changes can not simply be explained by the dysfunctions developing in the ovary, and the mechanism remains to be determined. The facts that GnRH neurons contain LH receptors and LH inhibits GnRH synthesis and secretion lead us to postulate that LH may play a role during reproductive senescence. The underlying mechanism on the effect of LH on GnRH synthesis during reproductive aging may result from the constantly elevated LH levels that feedback on the hypothalamus where LH binds to its receptors in GnRH neurons to inhibit GnRH synthesis. Alternatively, LH receptor levels may change with age and thus the sensitivity of GnRH neurons in response to the inhibitory effect of LH may be increased. The following two specific aims are designed to test our hypothesis using several well-established cellular and molecular biology techniques. (1) To determine LH receptor levels in GnRH neurons during reproductive aging. (2) To investigate the regulation of GnRH gene expression by LH during reproductive aging. Since GnRH is at the top of the endocrine hierarchy regulating mammalian reproduction and also has a number of other physiological functions, determining the factors that contribute to age-related alteration of GnRH neuronal functions will greatly advance our current knowledge of reproductive senescence.